Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.
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PMID:Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. 939 48

Oxidative stress has been suggested to play a central role in the pathogenesis of lung fibrosis and lung epithelial cell apoptosis is considered to be a key event during fibrogenesis. Studies from various laboratories have indicated that metabolic conditions may initiate oxidative stress, thereby contributing to epithelial cell death. This study was designed to test the hypothesis that glyoxal, an intermediate product in the glycation reaction leading to advanced glycation end products (AGEs), may induce lung epithelial cell apoptosis. We investigated the in vitro effects of glyoxal on fetal human lung epithelial L132 cells. Immunocytochemical analysis of paraffin-embedded cells and fluorescence-activated cell sorter analysis revealed a dose-dependent accumulation of the glycoxidation product (epsilon)N-carboxymethyllysine (CML) in all compartments of the cell. It has been shown that CML modification of proteins may serve as an indicator for oxidative stress. To examine the role of apoptosis in epithelial lung cells we investigated glyoxal-dependent changes in pro- and antiapoptotic mediators bax and activated caspase-3, and galectin-3 and bcl-2, respectively. Increasing concentrations of glyoxal (50 to 400 microM) induced an increase in the number of apoptotic cells. The apoptotic changes were confirmed by transmission electron microscopy. Immunocytochemical analysis of treated cells revealed the presence of other AGEs such as pentosidine as well as products of lipid peroxidation.
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PMID:Induction of apoptosis by glyoxal in human embryonic lung epithelial cell line L132. 1101 13

Owing to their relevance for growth regulation and cell adhesion monitoring the expression of galectins (endogenous beta-galactoside-binding lectins) and their binding sites has relevance for tumor biology. Using galectin-type-specific reagents (non-crossreactive antibodies for proto-type galectin-1, chimera-type galectin-3 and tandem-repeat-type galectins-4 and -8, and labeled galectins-1, -3, and -4) we determined galectin expression in cutaneous T cell lymphomas (CTCL) and controls. In addition to commonly studied galectins-1 and -3, tandem-repeat-type galectins could be detected, i.e., galectin-8 in six from 15 cases and galectin-4 in one of 15 cases. In view of relevant ligands such as bcl-2 or integrins the presence of galectins-3 and -8 seems to be possibly related to loss of proliferation control and change in cell adhesion properties that are involved in clonal expansion and epidermal spread of malignant T cell clones. Successful chemotherapy of CTCL alters galectin expression selectively as shown for liposomal doxorubicin.
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PMID:Galectin fingerprinting by immuno- and lectin histochemistry in cutaneous lymphoma. 1186 81

We investigated the role of galectin-3 in metastasis of human breast carcinoma BT549 cells using the experimental liver metastasis model. Underlying mechanisms were then elucidated using the liver/tumor co-culture and cell culture systems. After intrasplenic injection, galectin-3 cDNA transfected BT549 cells (BT549(gal-3 wt)) formed metastatic colonies in the liver, while galectin-3 null BT549 cells (BT549(par)) did not, demonstrating that galectin-3 enhances metastatic potential. More than 90% of BT549(gal-3 wt) cells survived after 24 hours-co-culture with the liver fragments isolated following ischemia treatment. In contrast, more than half of BT549(par) cells showed metabolic death following co-culture with the liver fragments. When the liver from inducible nitric oxide synthase (iNOS) knockout mice was used, no cytotoxicity to BT549(par) cells was observed. Thus, iNOS exerts cytotoxicity on BT549(par) cells and galectin-3 can protect against iNOS-induced cytotoxicity. BT549(gal-3 wt) also exhibited enhanced survival against peroxynitrite (up to 400 micromol/L) in vitro. A single mutation in the NWGR motif of galectin-3 obliterated both metastatic capability and cell survival, indicating that the antiapoptotic function of galectin-3 is involved in enhanced metastasis. In conclusion, galectin-3 enhances the metastatic potential of BT549 cells through resistance to the products of iNOS, possibly through its bcl-2-like antiapoptotic function.
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PMID:Role of galectin-3 in breast cancer metastasis: involvement of nitric oxide. 1189 Dec 3

The aim of this study was to glyco- and immunohistochemically analyze expression of distinct growth/adhesion-related markers of primary testicular carcinomas and their lung metastases in relation to the risk of developing lung metastases and survival of patients, and to correlate immunohistochemical staining profile and syntactic structure analysis in order to delineate new prognostic parameters for this tumor type. Clinical features of 50 patients with primary testicular carcinomas and their corresponding lung metastases were evaluated and compared to those of a control cohort of 25 cases. The set of eight probes including labeled galectins-1 and -3, specific non-cross-reactive antibodies against galectins-1, -3, and -8 as well as anti-Ki-67, anti-bcl-2, and anti-p53 was applied to formalin-fixed, paraffin-embedded tumor sections of both primary and metastatic lesions. Syntactic structure analysis computed staining intensities and structural features of the tumor cells. These parameters were set into relation separately and in combination to clinical data including tumor stages, smoking habits, applied cytostatic therapy, disease-free interval, and survival. The risk of testis cancer patients to develop lung metastases depends in descending order on the tumor cell type (non-seminoma versus seminoma), tumor cell heterogeneity (mixed versus monomorphous cell type), age of patients, and pT stage. The extent of differential expression of galectin-related features between primary and secondary lesions was pronounced. Prognostic correlations for distinct galectin-related features were delineated in combination with data from syntactic structure analysis, for example cluster radius of galectin-3-positive tumor cells and post-surgical and total survival. Lengths of disease-free interval and total survival of patients were also correlated to characteristics obtained by syntactic structure analysis and their combination with galectin data in the first place, then to smoking habits, percentage of proliferating cells in the primary and secondary tumors, and finally to expression of certain galectins and of p53. Patients with non-seminoma testicular cancer should be thoroughly controlled for lung metastases. Regarding marker selection, our study underscores that further investigation of the growth-regulatory network of galectins is clearly warranted.
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PMID:Combined analysis of tumor growth pattern and expression of endogenous lectins as a prognostic tool in primary testicular cancer and its lung metastases. 1279 89

The expression of transcripts for anti-apoptotic (survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1 and bcl-2) and pro-apoptotic (bax-alpha) genes, and for multiple drug resistance related protein-1 (MRP-1) gene were investigated, using RT-PCR, in 106 breast tumour biopsies. Normal breast tissue was also analysed for comparative purposes. Overall, survivin, survivin-deltaEx3, survivin-2B, bcl-2, bag-1, galectin-3, bax-alpha and MRP-1 mRNAs were detected in 68, 54.7, 9.4, 78.4, 80.9, 98.9, 97.8 and 72.8%, respectively, of tumour specimens. Uniquely among the mRNAs analysed, the expression of bcl-2 correlated significantly with disease outcome, with bcl-2 expression indicative of favourable outcome in terms of both relapse-free survival and overall survival. This suggests that bcl-2 mRNA expression may be a key prognostic marker for breast cancer and that routine analysis of expression of this transcript should be considered. The results from this study suggest, however, that the expression of survivin, survivin-deltaEx3, survivin-2B, bag-1, galectin-3, bax-alpha and MRP-1 mRNAs cannot be considered as prognostic indicators of disease outcome for patients with breast cancer.
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PMID:Lack of prognostic significance of survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1, bax-alpha and MRP-1 mRNAs in breast cancer. 1460 38

We studied a series of 10 solid cell nests (SCNs) of the thyroid and a case of cystic tumor of the atrioventricular node (CTAVN) of the heart and reviewed the literature. The CTAVN and SCNs appeared as cystic and/or solid (squamoid) structures mainly composed of polygonal or oval cells (main cells) admixed with occasional clear cells (neuroendocrine and C cells). Main cells were immunoreactive for simple and stratified epithelial-type cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. Neuroendocrine (and C) cells were positive for simple-type cytokeratins, carcinoembryonic antigen, calcitonin, chromogranin, synaptophysin, and thyroid transcription factor-1. Our data support the hypothesis that the CTAVN of the heart and the SCNs of the thyroid are identical structures that represent the same lesional process. The assumption that CTAVN is a ultimobranchial heterotopia fits with the known role of cardiac neural crest cells in cardiovascular development.
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PMID:Cystic tumor of the atrioventricular node of the heart appears to be the heart equivalent of the solid cell nests (ultimobranchial rests) of the thyroid. 1571 32

Solid cell nests (SCNs) of the thyroid are single or multiple foci of solid and/or cystic clusters of squamoid cells (main cells) with a minor proportion of C-cells, found in the normal thyroid. The SCNs have also been reported in the heart as an ultimobranchial heterotopia. Here, the authors describe a case of thyroid-type SCNs associated with struma ovarii. Main cells were positive for simple and stratified epithelial-type cytokeratins, carcinoembryonic antigen, carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. The neuroendocrine cell population was positive for chromogranin A and synaptophysin but negative for calcitonin, suggesting a common ancestor cell capable of dual differentiation toward thyroid follicular cells and hindgut-type endocrine cells. The existence of thyroid-type SCNs in struma ovarii could be easily understood by considering the struma ovarii as a teratoma; at the same time, these findings also support the idea of a close histogenetic link between the main cells of SCNs and thyroid tissue.
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PMID:Thyroid-type solid cell nests in struma ovarii. 2003 83

Galectin-3 belongs to a family of carbohydrate-binding proteins whose function is not fully characterized. However, it is believed to play a role in adhesion, proliferation and apoptosis in solid tumors. We aimed at investigating galectin-3 expression in bladder cancer. Galectin-3 expression was assessed by transcript profiling (U133A arrays) in a series or frozen bladder tumors (n = 105). Immunohistochemistry was performed on tissue arrays containing bladder tumors (n = 389) to evaluate associations of protein expression patterns of galectin-3 with proliferation (Ki67), apoptosis (apopdetek), bcl-2, and clinicopathologic variables. Galectin-3 protein levels were then quantified in 160 urinary specimens of bladder cancer patients and controls by enzymeimmunoanalysis. Galectin-3 gene expression levels increased in invasive tumours as compared with non-muscle invasive lesions (p = 0.001) and were associated with poor survival in patients with advanced disease (p = 0.03). Protein expression patterns also correlated galectin-3 with tumor stage (p < 0.001), grade (p = 0.03), Ki67 and apopdetek (p < 0.001), and overall survival in patients with T1G3 tumors (p < 0.001). Furthermore, galectin-3 urinary levels segregated bladder cancer patients from controls with high diagnostic accuracy (AUC = 0.7). Independent series of bladder tumors showed that transcript and protein levels of galectin-3 were differentially expressed along bladder cancer progression. Urinary protein levels served to identify bladder cancer patients. These observations suggest a role for galectin-3 as a biomarker for bladder cancer diagnostics, staging, and outcome prognosis.
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PMID:Galectin-3 expression is associated with bladder cancer progression and clinical outcome. 2040 58

Pituicytomas are neoplasms that arise from pituicytes, which are specialized glia of the posterior pituitary. Pituicytes have 5 ultrastructural variants: light, dark, granular, ependymal, and oncocytic. Granular cell tumors of the pituitary gland are thought to arise from granular pituicytes. Spindle cell oncocytomas are considered to arise from folliculostellate cells, which are sustentacular cells of the adenohypophysis. Recent data suggest that, whereas pituicytes and all 3 tumor types are positive for TTF-1, folliculostellate cells are negative for TTF-1. We investigated 7 spindle cell oncocytomas, 4 pituicytomas, and 3 granular cell tumors for their genetic (BRAF(V600E) mutation and BRAF-KIAA fusion), immunohistochemical (GFAP, vimentin, S100 protein, olig2, IDH1-R132H, NF, galectin-3, chromogranin-A, CD56, EMA, CAM5.2, CD68, TTF-1, and bcl-2), and ultrastructural features to refine their classification. All tumors had nuclear positivity for TTF-1 and were negative for CAM5.2, chromogranin-A, and NF. GFAP, vimentin, S100, galectin-3, EMA, and CD68 were variably positive in the majority of the 3 tumor groups. Olig2 was only positive in 1 pituicytoma. Whereas granular cell tumors were negative for bcl-2 and CD56, pituicytomas and spindle cell oncocytomas showed variable positivity. All tumors were negative with the IDH1-R132H mutation-specific antibody, and none had evidence of BRAF alterations (BRAF(V600E) mutation and BRAF-KIAA fusion). Diffuse TTF-1 expression in nontumorous pituicytes, pituicytomas, spindle cell oncocytomas, and granular cell tumors indicates a common pituicyte lineage. The ultrastructural variants of pituicytes are reflected in these 3 morphologic variants of tumors arising from these cells. We propose the terminology "oncocytic pituicytomas" and "granular cell pituicytomas" to refine the classification of these lesions.
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PMID:Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma. 2388 61


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